The present invention relates to fragrance compositions exhibiting antimicrobial activity with a hedonically acceptable odor. The present invention also relates to antimicrobial-flavor compositions which are capable of eliminating one or more microorganisms from a solid or semisolid surface (e.g., skin) or a three-space inhabited by said microorganisms, which compositions include salicylaldehyde and at least one organoleptically compatible antimicrobial synergism cofactor substance.
The prior art, including U.S. Pat. No. 5,965,518 issued on Oct. 12, 1999, the specification for which is incorporated by reference herein, indicates that fragrances having antimicrobial activity may comprise between 3 up to 20% by weight of non-aromatic terpenoids. U.S. Pat. No. 5,965,518 further indicates that the fragrance composition may also, either alternatively or additionally, include essential oils containing phenoic compounds as a major constituent and/or essential oils containing non-aromatic terpenoids as the main constituent. U.S. Pat. No. 5,965,518 further indicates that the fragrance composition further has an odor intensity index of less than 100 and an odor evaluation acceptability index of greater than 50.
Fragrances are commonly incorporated in a wide variety of household and industrial items, for example, counterwipes and cleansers, in order to impart a pleasing odor to a solid or semisolid surface or a three-space. A number of fragrances have been reported to have weak bacteria static activity. However, this activity has been ascertained to be too low to be of practical use. To overcome this weak activity and achieve antimicrobial fragrances of practical use either as bacteria static agents and preservatives or as bacteriacidal agents and sanitizers and disinfectants, combinations of fragrance materials with other materials are employed. For example, fragrances have been combined with a cationic phospholipid as taught in U.S. Pat. No. 5,420,104; and fragrances have been combined with a preservative and surface active agent as taught in U.S. Pat. No. 5,306,707.
Another possible way to achieve useful antimicrobial activity in fragrance compositions is to increase the effective fragrance ingredient concentration until the desired activity is achieved; for example, as described in U.S. Pat. No. 5,306,707 wherein a composition requires 30% of effective perfume ingredients in order to achieve antimicrobial activity in a household product. When using such products with such high fragrance concentrations, the aroma obtained is aesthetically displeasing and not acceptable to the consumer in the ultimate household product.
U.S. Pat. No. 5,965,518 issued on Oct. 12, 1999 attempts to overcome such objections by means of employing a mixture of 3-20% phenoic compounds and between 20-80% non-aromatic terpenoids, but does not specifically disclose the nature of the antimicrobial activity effected as a result of using such compositions and does not indicate which specific product compositions are effective against which specific microorganisms.
Accordingly, a need exists for the ability to create fragrance formulations having specific antimicrobial activity using fragrance formulations which are, in household products, capable of emitting aesthetically pleasing aromas and simultaneously, which are capable of eliminating specific microorganisms using such household products.
Nothing in the prior art sets forth fulfillment of such a need.
Our invention is directed to antmicrobial-fragrance compositions which are capable of eliminating one or more microorganisms from a solid or semisolid surface or three-space inhabited by such microorganisms. Such compositions consist essentially of (a) salicylaldehyde having the structure: 
and (b) at least one organoleptically compatible antimicrobial synergism cofactor substance, with the weight ratio of salicylaldehyde:cofactor substance being from about 1:10 up to about 10:1.
The degree of synergism of the mixture is ascertained according to the xe2x80x9cIFF Antimicrobial Synergism Testxe2x80x9d wherein the difference between the actual an expected antimicrobial values of the mixture is greater than or equal to a multiple of 0.05 and the expected antimicrobial value of the mixture.
The IFF Antimicrobial Synergism Test is based on observation and measurement of zones of inhibition against microorganisms such as:
Escherichia coli; 
Enterococcus hirae; 
Pseudomonas aeruginosa; 
Staphylococcus aureus; and
Saccharomyces cerevisae. 
Such measurements of zones of inhibition may be in the form of measurement of the average radius of such zones or of the actual areas of such zones of inhibition.
The measurement of xe2x80x9csynergismxe2x80x9d is based on a comparison of xe2x80x9cexpected valuexe2x80x9d of the dimension of the zone of inhibition shown by the symbol: xcex94E and the actual value of the zone of inhibition shown by the symbol: xcex94A. This difference: [xcex94Axcex94E], if greater than or equal to the synergism test constant, is indicative of such synergism. The inequality is shown thusly: xcex94Axe2x88x92xcex94Exe2x89xa7K or, when applied to the average diameters of zones of inhibition, are shown thusly: DAxe2x88x92DExe2x89xa7K. The expected value of the dimension or area of the zone of inhibition is calculated according to the following generalized equation:
xcex94E=xcexa3xcex4AifiA+xcexa3xcex4BifiB 
wherein the symbol: xcex4Ai is the zone of inhibition for a pure component; the symbol: xcex4Bi is the zone of inhibition for a second pure component; the symbol: fiA is the mole fraction or weight fraction of the first pure component in the mixture which is the subject of the synergism test; and the symbol: fiB is the weight fraction or mole fraction of the second component in the mixture which is the subject of the synergism test. When multiple components are being compared against one another, the equation:
xcex94Excexa3xcex4AifiA+xcexa3xcex4BifiB 
is used. More specifically, the calculation for the expected value as between, for example, salicylaldehyde and other components such as indole or ethyl vanillin, is according to the equation:
DE=fCDC+fSDS 
wherein the symbol: DE is the expected value of the diameter of the zone of inhibition for the mixture; the symbol: DC is the actual value of the diameter of the zone of inhibition for the pure added component; the symbol: DS is the diameter of the zone of inhibition for salicylaldehyde when used alone; the symbol: fC is the mole fraction or the weight fraction of the added component, e.g., indole or ethyl vanillin, in the mixture; and the symbol: fS is the mole fraction or weight fraction of the salicylaldehyde as used in the mixture. The expected value thus calculated, of the zone of inhibition for the mixture, is then compared with the actual value of the diameter or other dimension for the zone of inhibition according to the general inequality: xcex94Axe2x88x92xcex94Exe2x89xa7K or, with respect to diameters of zones of inhibition, the inequality: DAxe2x88x92DExe2x89xa7K. The value of K as stated, supra, for the data in the instant application, is the product of the expected value of the diameter of the zone of inhibition and 0.05 according to the equation: K=0.05DE. However, the value of the synergism test constant in general is calculated according to the following equation: K=(xcex94E)xcfx80 wherein the symbol: xcex94E is the expected value of the dimension of the zone of inhibition, e.g., diameter or area; and the term: xcfx80 is the xe2x80x9cpreselected confidence interval fraction,xe2x80x9d chosen, arbitrarily, in the instant application as 0.05. This value, however, may vary between 0.025 and 0.10.
The difference between actual dimension for antimicrobial inhibition and expected dimension for antimicrobial inhibition, [xcex94Axe2x88x92xcex94E], and the antimicrobial/olfactory synergism test constants K, is shown by the equation: xcex={[xcex94Axe2x88x92xcex94E]xe2x88x92K} in wherein the term: xcex, is a measure of the degree of synergism. Specifically, with respect to the situation where the dimension is the diameter of the zone of inhibition, the measure of the degree of synergism is shown thusly:
xcex={[DAxe2x88x92DE]xe2x88x92K}. 
When the measure of the degree of synergism is greater than zero, to wit: xcex greater than 0, under the constraints of the instant specification, synergism exists. On the other hand, when the degree of synergism is less than or equal to zero, to wit: xcexxe2x89xa60, then under the constraints of the instant specification, synergism does not exist.
We have found that various cofactor substances for use in combination with salicylaldehyde having the structure: 
are useful in the practice of our invention, to wit:
(i) phenolic compounds having the structure: 
wherein one or two of R1, R2, R3, R4 and R5 is the same or different C1-C3 alkyl and the other of R1, R2, R3, R4 and R5 is hydrogen;
(ii) benzyl alcohol having the structure: 
(iii) indole having the structure: 
(iv) ethyl vanillin having the structure: 
(v) orcinyl methyl ether having the structure: 
(vi) terpinenol having the structure: 
(vii) tetrahydrolinalool having the structure: 
More specifically, our invention is directed, inter alia, to a composition which is a broad spectrum antimicrobial fragrance composition capable of eliminating the microorganisms:
Escherichia coli; 
Enterococcus hirae; 
Pseudomonas aeruginosa; 
Staphylococcus aureus; and
Saccharomyces cerevisae 
from a solid or semi-solid surface or a three-space inhabited by such microorganisms comprising (a) salicylaldehyde having the structure: 
and (b) at least one organoleptically compatible antimicrobial synergism cofactor substance selected from the group consisting of:
(i) benzyl alcohol having the structure: 
(ii) indole having the structure: 
(iii) ethyl vanillin having the structure: 
(iv) terpinenol-4 having the structure: 
The weight ratios of salicylaldehyde:cofactor substance may vary between about 10:1 up to about 1:10, with a preferred weight ratio of 1:1.
Our invention is also directed to compositions capable of the elimination of the microorganisms:
Escherichia coli; 
Pseudomonas aeruginosa; 
Staphylococcus aureus; and
Saccharomyces cerevisae 
from a solid or semi-solid surface or three-space inhabited by such microorganisms comprising a mixture of (a) salicylaldehyde and (b) at least one organoleptically compatible antimicrobial synergism cofactor substance which is indole with the rate ratio of salicylaldehyde:indole varying from about 10:1 up to about 1:10, preferably about 1:1.
Furthermore, our invention is directed to a composition capable of eliminating the microorganism Saccharomyces cerevisae from a solid or semi-solid surface or three-space inhabited by said Saccharomyces cerevisae comprising (a) salicylaldehyde and (b) the organoleptically compatible antimicrobial synergism cofactor substance, thymol, having the structure: 
wherein the weight ratio of salicylaldehyde:thymol is from about 1:10 up to about 10:1.
Furthermore, our invention is directed to an antimicrobial-fragrance composition capable of eliminating the organisms:
Pseudomonas aeruginosa; 
Staphylococcus aureus; and
Saccharomyces cerevisae 
from a solid or semi-solid surface or three-space inhabited by such microorganisms comprising (a) salicylaldehyde having the structure: 
and (b) the organoleptically compatible antimicrobial synergism cofactor substance, p-cresol having the structure: 
wherein the weight ratio of salicylaldehyde:p-cresol is from about 10:1 up to about 1:10.
Furthermore, our invention is directed to an antimicrobial-fragrance composition capable of eliminating the microorganisms:
Staphylococcus aureus; and
Saccharomyces cerevisae 
from a solid or semi-solid surface or three-space inhabited by such microorganisms comprising a mixture of (a) salicylaldehyde having the structure: 
and (b) carvacrol having the structure: 
wherein the weight ratio of salicylaldehyde:carvacrol is from about 1:10 up to about 10:1.
Furthermore, our invention is directed to an antimicrobial-fragrance composition capable of eliminating the microorganisms:
Staphylococcus aureus; and
Saccharomyces cerevisae 
from a solid or semi-solid surface or three-space inhabited by such microorganisms comprising:
(a) salicylaldehyde;
(b) thymol;
(c) carvacrol; and
(d) p-cresol
wherein the weight ratios of salicylaldehyde:carvacrol:thymol:p-cresol is from about 1:1:1:1.
Our invention is also directed to a process for eliminating at least one of the microorganisms:
Escherichia coli; 
Enterococcus hirae; 
Pseudomonas aeruginosa; 
Staphylococcus aureus; and
Saccharomyces cerevisae 
from a solid or semi-solid surface or three-space inhabited by such microorganisms in a microorganism-eliminating concentration and quantity, a composition which is a mixture of (a) salicylaldehyde and (b) at least one organoleptically compatible antimicrobial synergism cofactor substance selected from the group consisting of:
(i) at least one phenolic compound having the structure: 
wherein one or two of R1, R2, R3, R4 and R5 is C1-C3 alkyl and the other of R1, R2, R3, R4 and R5 is hydrogen;
(ii) benzyl alcohol;
(iii) indole;
(iv) ethyl vanillin;
(v) orcinyl methyl ether having the structure: 
(vi) terpinenol-4 having the structure: 
(vii) tetrahydrolinalool having the structure: 
The compositions of our invention have application in all-purpose cleaning compositions, gel-type toilet rim articles, liquid-type toilet rim articles, personal shower cleaning compositions, and body and hair care products including but not limited to shower gel compositions, shampoo compositions and foam bath compositions, the formulations for which are well known to those having ordinary skill in the art.
The following substances are representative of products wherein our compositions have found significant utility and efficacy:
(i) DOVE(copyright) (tradmark of Lever Brothers Company, New York, N.Y.), moisturizing body wash, the composition for which is set forth in U.S. Pat. Nos. 5,085,857 and 5,415,810, the specifications for which are incorporated by reference herein (ingredients: water, cocamidopropyl betane, dimethacone, sodium cocoyl isethionate, sodium laureth sulfate, ammonium sulfate, laureth-4, laureth-23, titanium dioxide and guar hydroxypropyltrimonium chloride);
(ii) bagnoschiuma bath foam (contents: water, sodium laureth sulfate, sodium chloride, lauramidopropyl betaine, methylisothiazolinone and methylchloroisothiazolinone);
(iii) AJAX(copyright) (trademark of the Colgate Palmolive Company of New York, N.Y.), dish liquid; and
(iv) ALBERTO VO5(copyright) (trademark of the Alberto-Culver U.S.A., Inc. Company of Melrose Park, Ill.) (contents: water, sodium lauryl sulfate, lauramide diethanolamine, sodium chloride, glycerine, retinyl palmitate, ascorbic acid, tocopheryl acetate, panthenol, ergocalciferol, corn oil, hydroxypropyl cellulose, phosphoric acid, cocamide diethanolamine, sodium laureth sulfate and DMDM hydantoin).
The compositions of our invention have also found use and are effective as antimicrobials in the formulations as exemplified in U.S. Pat. No. 5,879,666 issued on Mar. 9, 1999, the specification for which is incorporated by reference herein.
The following Table I sets forth the organoleptically compatible antimicrobial synergism cofactor substance; the microorganism(s) against which the substances are effective; and the degree of synergism of the mixture and data supporting same.
We have also ascertained a relationship to the molecular weight of the organoleptically compatible antimicrobial synergism cofactor substance used in admixture with the salicylaldehyde in the compositions of our invention versus the degree of synergism, xcex, and this relationship is set forth in the following Table II for Saccharomyces cerevisae. The following Table II is illustrated in accompanying FIG. 1, described herein briefly and in detail, infra. The plot in FIG. 1, infra, is that of the term: xcexc vs. xcex,
wherein xcexc is a function of the molecular weight of the cofactor, thusly described:   μ  =            1      10        ⁡          [              MW        -        100            ]      
wherein MW is the molecular weight of the cofactor.
Our invention is also directed to a process for augmenting or enhancing the aroma of a consumable material selected from the group consisting of perfume compositions, colognes and perfumed articles while simultaneously imparting thereto antimicrobial properties comprising the step of admixing a consumable material base with (i) an antimicrobial-imparting quantity and concentration of a composition consisting essentially of (a) salicylaldehyde and (b) at least one organoleptically-compatible antimicrobial synergism cofactor substance with the weight ratio of salicylaldehyde:cofactor substance being from about 1:10 up to about 10:1; and (2) an aroma imparting concentration and quantity of an organoleptically-compatible perfume composition.
Such organoleptically-compatible perfume compositions consist of natural essential oils and synthetic materials. Examples of the natural and synthetic oils useful in the practice of our invention are as follows:
bitter almond;
angelica;
basil;
bergamot;
chamomile;
caraway;
celery;
citronella;
coriander;
estragon;
fennel;
ginger;
lavender;
lime;
mandarin;
melissa;
nutmeg;
bitter orange;
pepper;
peppermint;
rosemary;
spike;
valerian;
sweet almond;
anise;
bay;
cananga;
cardamom;
cinnamon;
clove;
dill;
eucalyptus;
geranium;
laurel;
lemon;
mint;
orange;
parsley;
pimento;
rose;
sage;
sassafras;
thyme; and
verbena.
The following synthetic materials are useful in the practice of our invention:
allyl amyl glycolate;
benzaldehyde;
cis-3-hexenyl acetate;
dihydromyrcenol;
n-decyl aldehyde;
methylionone;
trans,trans-xcex4-damascone;
xcex2-ionone;
xcex1-ionone;
xcex2-damascenone;
xcex3-damascenone;
p-t-butyl-xcex1-methylhydrocinnamicaldehyde;
o-t-butylcyclohexyl acetate;
i-nonyl acetate;
xcex2-phenylethyl alcohol;
xcex1-phenylethyl alcohol;
xcex2-phenylethyl acetate;
xcex2-phenylethylisobutyrate;
xcex2-phenylethylcinnamate;
dimethylbenzylcarbinyl acetate; and
isobutylbenzoate.
The antibacterial compositions of our invention are useful in conjunction with perfume compositions in the ratio of from about 0.1% up to about 10% by weight of the perfume composition.
The antibacterial compositions of our invention are useful in conjunction with perfumed articles of our invention at a percentage of from about 0.001% up to about 5% by weight of the perfumed article, with a preferred percentage of from about 0.01% up to about 2% by weight.
Our invention is also directed to the creation of electronic data processing software designed to yield information for indication of antimicrobial synergism for a fragrance-antibacterial formulation or for a perfumed article-antibacterial formulation. The means for the creation of such software comprises:
(a) means for the ascertainment of specific antimicrobial-fragrance or perfumed article components, which individually eliminate given microorganisms on a solid or semi-solid surface or in a three-space inhabited by said microorganisms, measured by xcex4Ai or xcex4Vi, with associated data input to the memory of a computer server;
(b) means for formulating one or more mixtures of said specific antimicrobial fragrance or perfumed article components of (a) having weight fractions or mole fractions of components, fiA and fiB, with associated data input to the memory of a computer server;
(c) means for ascertainment of data indicative of antimicrobial activity of the mixtures of (b), xcex94A, with associated data input to the memory of the computer server;
(d) means for calculation of the expected value, xcex94E, of antimicrobial activity of the mixtures of (b) using the inputted, stored memory data of (a) [xcex4Ai and xcex4Bi] and (b) [fiA and fiB] according to the algorithm: xcex94E=xcexa3xcex4AifiA+xcexa3xcex4BifiB;
(e) means for storing in the computer memory, the data required for calculation of k, the IFF antimicrobial/olfactory synergism test constant, which is the product of xcfx80, a preselected confidence interval fraction (e.g., a number from about 0.005 up to about 0.1, preferably 0.05 and xcex94E);
(f) means for ascertainment of the difference, [xcex94Axe2x88x92xcex94E], and the product, K=*xcex94E)xcfx80, with associated data input;
(g) means for instructing the setting of a system to accept a formulation in the event of: xcex94Axe2x88x92xcex94Exe2x89xa7K or: xcex greater than 0, and reject a formulation in the event of: xcexxe2x89xa60, wherein, xcex (the measure of the degree of synergism) is defined thusly: xcex={[xcex94Axe2x88x92xcex94E]xe2x88x92K}; and
(h) means for instructing the repeating of steps (a)-(g), inclusive, in the event of a result of: xcexxe2x89xa60.
The protocols for the screenings of the organoleptically-compatible antimicrobial synergism cofactor substances, taken alone or taken in conjunction with the salicylaldehyde of our invention, are as follows:
Preparation of Microorganism Cultures:
Isosensitest agar was made by dissolving 31.4 grams of agar in 1 liter of distilled water. 10 Ml of molten agar was added to universal bottles and allowed to set at an angle to produce a slope. The bacteria were then subcultured onto the slopes individually.
Isosensitest broth was made up by dissolving 23.4 grams of powder in 1 liter of distilled water. 10 Ml of broth were then added to universal bottles.
For Saccharomyces cerevisae, malt extract agar (50 grams in 1 liter) and malt extract broth (20 grams in 1 liter) was used instead. The isosensitest agar and broth were autoclaved at 121xc2x0 C. for 15 minutes. The malt extract agar and broth were autoclaved at 115xc2x0 C. for 10 minutes.
Cells from cultures grown on the isosensitest agar and malt extract agar were inoculated the night before the agar diffusion technique was scheduled, using a sterile loop, into fresh isosensitest broth and malt extract broth and incubated overnight at 30xc2x0 C. The final concentration was 106 mlxe2x88x921.
Agar Diffusion Technique:
0.5 Ml of a single test microorganism was then pipetted per sterile petri dish and 20 ml amounts of molten isosensitest agar and malt extract agar at 45xc2x0 C. were then added. The plates were then agitated to ensure mixing of the agar and microorganism without creating bubbles. After setting, 4 mm wells were punched in the center of each plate using a pharmacia gel punch.
Aroma chemicals at 10 xcexcl (of pure undiluted substance as supplied, or if a solid, diluted as indicated in an appropriate volume of solvent) were applied to the wells. After 30 minutes, having allowed diffusion of the sample throughout the agar, the plates were inverted and incubated at 30xc2x0 C. for 48 hours. Zones of inhibition were measured using vernier calipers. Each aroma chemical was tested in duplicate against all five microorganisms.
As olfactory agents, the antibacterial/fragrance compositions of our invention can be formulated into or used as components of a xe2x80x9cperfume compositionxe2x80x9d or can be used as components of a xe2x80x9cperfumed articlexe2x80x9d or the antibacterial/perfume composition may be added to perfumed articles.
The term xe2x80x9cperfume compositionxe2x80x9d is used herein to mean a mixture of organic compounds including, for example, alcohols, aldehydes, ketones, nitrites, ethers, lactones, natural essential oils, synthetic essential oils, esters and frequently, hydrocarbons which are admixed so that the combined odors of the individual components produce a pleasant or desired fragrance. Such perfume compositions usually contain (a) the main note or the xe2x80x9cbouquetxe2x80x9d or foundation stone of the composition; (b) modifiers which round off and accompany the main note; (c) fixatives which include odorous substances which lend a particular note to the perfume throughout all stages of evaporation, and substances which retard evaporation; and (d) topnotes which are usually low-boiling, fresh-smelling materials.
In perfume compositions, the individual component will contribute its particular olfactory characteristics, but the overall effect of the perfume composition will be the sum of the effects of each of the ingredients. Thus, the antibacterial/perfume compositions of this invention or mixtures thereof can be used in and of themselves to alter the aroma characteristics of a perfume composition, for example, by highlighting or moderating the olfactory reaction contributed by another ingredient in the composition.
The amount of at least one of the compositions of our invention, which will be effective in perfume compositions, depends on many factors, including the other ingredients, their amounts and the effects which are desired. It has been found that perfume compositions containing as little as 0.05% of at least one of the antibacterial/perfume compositions of our invention, or even less, can be used to impart interesting herbaceous, citusy, spicy, floral, sweet and vanillin aromas with earthy, musty and green undertones to soaps, solid and liquid anionic, cationic, nonionic or zwitterionic detergents, cosmetics, powders, liquid and solid fabric softeners, optical brightener compositions and other products. The amount employed can range up to 50% or higher and will depend on considerations of cost, nature of the end product and the effect desired on the finished product and particular fragrance sought.
The antibacterial/perfume compositions of our invention can be used alone or in a perfume composition as an olfactory component in detergents and soaps; space odorants and deodorants; perfumes, colognes, toilet waters; bath salts; hair preparations such as lacquers, brilliantines, pomades and shampoos; cosmetic preparations such as creams, deodorants, hand lotions and sun screens; powders such as talcs, dusting powders, face powders; and the like.
When used as an olfactory component of a perfumed article, as little as 0.005% of one or more of the antibacterial/perfume compositions of our invention will suffice, for example, to impart an interesting herbaceous, citrusy, spicy, floral, sweet, vanillin aroma with earthy, musty and green undertones. Generally, no more than 0.5% is required. Thus, the percentage in perfumed articles of the antibacterial/perfume compositions of our invention range from 0.005% up to about 0.5% based on the weight of a perfumed article.
In addition, the antibacterial/perfume compositions of our invention can contain a vehicle or carrier for one or more of the antibacterial/perfume compositions of our invention, taken alone or taken together with other ingredients. The vehicle can be a liquid such as alcohol, such as ethanol; a glycol, such as propylene glycol; or the like. The carrier can be an absorbent solid such as a gum or components for encapsulating the composition such as gelatin which can be used to form a capsule wall surrounding the perfume/antibacterial composition as by means of coacervation, or it can be a microporous polymer onto which the antibacterial/perfume composition of our invention is adsorbed.
It will be thus apparent that one or more of the antibacterial/perfume compositions of our invention can be utilized to alter, modify, augment or enhance sensory properties, particularly organoleptic properties such as fragrances of a wide variety of consumable materials.